Stem cells have been obtained from sources such as embryonic tissues, cord blood and other sources. U.S. Pat. No. 6,200,806 describes pluripotent stem cells obtained from human embryonic tissue. Such cells are capable of proliferating in vitro without significant karyotype changes while maintaining a capacity to differentiate into endoderm, mesoderm, and ectoderm tissues. These cells are negative for the SSEA-1 marker, positive for the SSEA-4 marker, express alkaline phosphatase activity and are pluripotent. These cells have euploid karyotypes and none of the chromosomes are obviously altered.
U.S. Pat. No. 5,843,780 describes a purified preparation of primate embryonic stem cells that is capable of proliferation in an in vitro culture for and maintains a karyotype in which all the chromosomes characteristic of the primate species are present and not noticeably altered through prolonged culture. These cells maintain a potential to differentiate into derivatives of endoderm, mesoderm, and ectoderm tissues throughout the culture. These cells will typically not differentiate when cultured on a fibroblast feeder layer and they can differentiate to trophoblasts and produce chorionic gonadotropin when cultured at a high density.
Pluripotent cells have been obtained from preimplantation embryos of several animals, e.g., Evans, et al., Theriogenology 33(1):125-128, 1990; Evans, et al., Theriogenology 33(1):125-128, 1990; Notarianni, et al., J. Reprod. Fertil. 41(Suppl.):51-56, 1990; Giles, et al., Mol. Reprod. Dev. 36:130-138, 1993; Graves, et al., Mol. Reprod. Dev. 36:424-433, 1993; Sukoyan, et al., Mol. Reprod. Dev. 33:418-431, 1992; Sukoyan, et al., Mol. Reprod. Dev. 36:148-158, 1993; Iannaccone, et al., Dev. Biol. 163:288-292, 1994).
Human embryonic carcinoma cells, which are pluripotent cells obtained from teratocarcinomas resemble human embryonic stem cells (Andrews, et al., Lab. Invest. 50(2):147-162, 1984; Andrews, et al., in: Robertson E., ed. Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, Oxford: IRL press, pages 207-246, 1987). Embryonic carcinoma cells can be induced to differentiate in culture, which is characterized by the loss of specific cell surface markers (SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81) and the appearance of new markers.
Stem cell populations and methods to use them have also been described elsewhere, see, e.g., U.S. Pat. Nos. 5,453,357, 6,986,887, 6,936,281, 6,967,029 and 6,872,389. Methods to obtain quantities of stem cells sufficient for treating clinical conditions are typically relatively expensive and complicated.
There is a current need for cost-effective methods for obtaining stem cells and using them to treat ameliorate various diseases associated with tissue or organ damage such as cardiovascular diseases, pulmonary conditions, neurological disorders, trauma, blood cell deficiencies and immune suppression conditions associated with aging or other causes. The invention provides methods to accomplish these. The use of these agents can be combined with one or more conventional treatments for these disorders.